Prenatal diagnosis of VACTERL syndrome and partial caudal regression syndrome: a previously unreported association.
ABSTRACT We describe a case of VACTERL syndrome associated with type 1 unilateral caudal regression syndrome. The abnormal sonographic findings at 26 weeks included hemivertebrae, scoliosis, hypoplastic and deformed lumbar spine and sacrum, preaxial polydactyly on the left hand, duplicated hallux on the left foot and hemihypoplasia of the left lower limb, bilateral club foot, and single umbilical artery. Postmortem examination confirmed prenatal sonographic findings with additional findings of supernumerary rib at the lumbar level and anal atresia.
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Article: VACTERL/VATER Association.[Show abstract] [Hide abstract]
ABSTRACT: VACTERL/VATER association is typically defined by the presence of at least three of the following congenital malformations: vertebral defects, anal atresia, cardiac defects, tracheo-esophageal fistula, renal anomalies, and limb abnormalities. In addition to these core component features, patients may also have other congenital anomalies. Although diagnostic criteria vary, the incidence is estimated at approximately 1 in 10,000 to 1 in 40,000 live-born infants. The condition is ascertained clinically by the presence of the above-mentioned malformations; importantly, there should be no clinical or laboratory-based evidence for the presence of one of the many similar conditions, as the differential diagnosis is relatively large. This differential diagnosis includes (but is not limited to) Baller-Gerold syndrome, CHARGE syndrome, Currarino syndrome, deletion 22q11.2 syndrome, Fanconi anemia, Feingold syndrome, Fryns syndrome, MURCS association, oculo-auriculo-vertebral syndrome, Opitz G/BBB syndrome, Pallister-Hall syndrome, Townes-Brocks syndrome, and VACTERL with hydrocephalus. Though there are hints regarding causation, the aetiology has been identified only in a small fraction of patients to date, likely due to factors such as a high degree of clinical and causal heterogeneity, the largely sporadic nature of the disorder, and the presence of many similar conditions. New genetic research methods offer promise that the causes of VACTERL association will be better defined in the relatively near future. Antenatal diagnosis can be challenging, as certain component features can be difficult to ascertain prior to birth. The management of patients with VACTERL/VATER association typically centers around surgical correction of the specific congenital anomalies (typically anal atresia, certain types of cardiac malformations, and/or tracheo-esophageal fistula) in the immediate postnatal period, followed by long-term medical management of sequelae of the congenital malformations. If optimal surgical correction is achievable, the prognosis can be relatively positive, though some patients will continue to be affected by their congenital malformations throughout life. Importantly, patients with VACTERL association do not tend to have neurocognitive impairment.Orphanet Journal of Rare Diseases 08/2011; 6:56. · 4.32 Impact Factor
Article: Caudal regression syndrome.Journal of Obstetrics and Gynaecology 02/2013; 33(2):202-3. · 0.55 Impact Factor
Prenatal Diagnosis of VACTERL Syndrome
and Partial Caudal Regression Syndrome:
A Previously Unreported Association
Ali Gedikbasi, MD,1Kanay Yararbas, MD,2Gokhan Yildirim, MD,1Dogukan Yildirim, MD,1
Oguz Arslan, MD,1Ahmet Gul, MD,1Yavuz Ceylan, MD1
1Department of Obstetrics and Gynecology, Perinatology Unit, Istanbul Bakirkoy Maternity and
Children Diseases Hospital, Istanbul, Turkey
2Division of Medical Genetics, Istanbul Bakirkoy Maternity and Children Diseases Hospital, Istanbul, Turkey
Received 17 November 2008; accepted 1 April 2009
ABSTRACT: We describe a case of VACTERL syn-
drome associated with type 1 unilateral caudal
regression syndrome. The abnormal sonographic
findings at 26 weeks included hemivertebrae, scolio-
sis, hypoplastic and deformed lumbar spine and sac-
rum, preaxial polydactyly on the left hand, duplicated
hallux on the left foot and hemihypoplasia of the left
lower limb, bilateral club foot, and single umbilical ar-
tery. Postmortem examination confirmed prenatal
sonographic findings with additional findings of su-
pernumerary rib at the lumbar level and anal
atresia. V V
sound 00:000–000, 2009; Published online in Wiley
C 2009 Wiley Periodicals, Inc. J Clin Ultra-
Keywords: VACTERL syndrome; partial caudal reg-
ression syndrome; prenatal diagnosis; ultrasono-
graphy; fetal malformations
from impaired development of the mesoderm.
The etiology of these rare syndromes is unclear,
but environmental factors and/or underlying
genetic predisposition have been incriminated.
Both syndromes have some common clinical fea-
tures and involve a wide spread of anomalies of
multiple systems. Ultrasound (US) diagnosis is
essential to determine the severity of the lesions
because of the poor prognosis.
ACTERL syndrome and caudal regression
syndrome (CRS) are both believed to result
A 38-year-old multigravid woman was first seen
at 26 weeks of gestation at our perinatology unit
for detailed US examination. Her obstetrical his-
tory was unremarkable with 11st-trimester abor-
tion and a healthy live birth at term. Family his-
tory was also uneventful. Detailed US examina-
tion performed with a Voluson 730 Expert and a
2.0–7.0-MHz probe (GE Healthcare; Milwaukee,
WI) revealed a single female fetus with scoliosis,
hemivertebrae, hypoplasia and deformity of the
thoracic and lumbar spine and sacrum, preaxial
polydactyly on the left hand, duplicated hallux on
the left foot, hemihypoplasia of the left lower
limb, bilateral club foot, and single umbilical ar-
tery (Figure 1). Fetal echocardiography and cra-
nial US were normal. Fetal biometry was consist-
ent with gestational age, and amniotic fluid vol-
ume was normal. Maternal blood analysis and
glucose levels were in normal ranges, with a nor-
mal 50 g oral glucose tolerance test.
Parents opted for termination of pregnancy
but refused cordocentesis or any genetic study. A
female fetus weighing 858 g was delivered.
Anteroposterior and lateral spine radiographs
showed abnormal lumbar spine with hemiverte-
brae and scoliosis and right supernumerary ribs
Postmortem pathologic examination of the
fetus confirmed prenatal findings. In addition,
there was discordant pelvis development and hy-
poplasia of left pelvis and left lower limb with
severe atrophy. The left knee was in flexion con-
tracture, and the left foot was hyperextended and
Correspondence to: A. Gedikbasi
' 2009 Wiley Periodicals, Inc.
VOL. 00, NO. 0, MONTH 2009
rotated, although it was not a classic clubfoot.
Right clubfoot was evident. Preaxial polydactyly
on the left hand, duplicated hallux on the left
foot, and supernumerary rib at the lumbar level
on the right were noted (Figure 3). An evident
hemivertebrae with scoliosis and hypoplasia of
vertebral bodies at the lumbar spine and sacrum
and forming a hypoplastic pelvis were seen
(Figure 3D). The examination of the GI tract
revealed anal atresia.
In 1973, Quan and Smith1reported the VATER
association, which included vertebral anomalies,
anal atresia, tracheoesophageal fistula, renal
defects, and radial limb dysplasia. The further
observation of cardiac anomalies by Temtamy
and Miller2within a VATER cohort broadened
the definition, and the expanded acronym VAC-
TERL was coined by Kaufman3and Nora and
Nora4to include limb abnormalities. It is a mne-
monic for the systems and defects involved,
including V (vertebral anomalies), A (anal atre-
sia), C (cardiac anomalies), TE (tracheoesopha-
geal fistula or esophageal atresia), R (renal/uri-
nary anomalies), and L (limb defects).
The exact cause of VACTERL association is
currently unknown and is thought to be multifac-
torial, with approximately 1 in 5000 live births.4
Causal heterogeneity has been reported as the
most likely conclusion. First, it was supposed
that there was a deficiency in mesodermal pro-
gress in patients with the VATER syndrome.1,5
Khoury6suggested that a common denominator
of the association is imperfect mesodermal devel-
opment during embryogenesis due to a variety of
causes, environmental factors, or teratogens,
leading to overlapping presentations. An addi-
tional potential mechanism was the maternal use
FIGURE 1. Prenatal US examination. (A) Sagittal sonogram shows
defective structure of lumbar spine and sacrum with scoliosis and
hemivertebrae. (B) Sonogram shows duplicated hallux on the left
foot. (C) Hemihypoplasia of left lower extremity. Comparison of left
(left) and right (right) femurs shows the smaller size of the left femur.
FIGURE 2. Postmortem spine radiographs. (A) Anteroposterior view shows hypoplasia of lumbar and sacral segments, hemivertebrae, scoliosis,
and supernumerary ribs. (B) Lateral radiograph shows sacral hypoplasia and defective structure of lumbar vertebrae.
GEDIKBASI ET AL
JOURNAL OF CLINICAL ULTRASOUND
of sex hormones in the first trimester, which
might affect embryogenesis.3
There is no agreement in the literature regard-
ing the minimum diagnostic criteria for VAC-
TERL syndrome. While some investigators con-
sider the association of three or more of the VAC-
TERL anomalies as mandatory for diagnosis,6,7
others have made the diagnosis with only two of
the associated anomalies.5
Damian8reported about the mitochondrial NP
3243 (MELAS) mutation in the kidney tissue of
an individual with VACTERL association, which
was the first instance of a molecular abnormality
identified in an individual with VACTERL. Kim9
reported about mutant analyses of Gli genes,
which encode transcription factors mediating
Sonic hedgehog (Shh) signal transduction. They
observed that defective Shh signaling leads to a
spectrum of developmental anomalies in mice
strikingly similar to those of VACTERL.
We found no explanation for the defective devel-
opment of left distal limb in association with VAC-
TERL syndrome. CRS is a rare malformation first
published by Duhamel.10CRS is related with the
impaired development of the midposterior axis
mesoderm and is about 200 times more frequent
in patients with diabetes, which makes it the most
specific fetal malformation in maternal diabetes.
This syndrome associates vertebral agenesis of
variable levels with urinary and digestive malfor-
mations. Physical agents such as extremes of tem-
perature, trauma, or radiographs; several drugs
(including lithium and sulfamides); and several
maternal nutritional deficiencies (in vitamins A
and E) have all proven to be inductive of this mal-
formation.11,12Additionally, recent findings lead
to the hypothesis that the pathogenesis of CRS
results from a vascular ‘‘steal effect’’ by the former
vitelline artery, which then disappears in the em-
bryonic and fetal development.13
The present case shows that a VACTERL syn-
drome and CRS can coexist in pregnancy. The
final diagnosis must be made by karyotype study,
careful family history, attentive second-trimester
US examination, and autopsy studies.
1. Quan L, Smith DW. The VATER association. Verte-
bral defects, anal atresia, T-E fistula with esopha-
geal atresia, radial and renal dysplasia: a spec-
trum of associated defects. J Pediatr 1973;82:104.
2. Temtamy SA, Miller JD. Extending the scope of
the VATER association: definition of the VATER
syndrome. J Pediatr 1974;85:345.
3. Kaufman RL. Birth defects and oral contracep-
tives. Lancet 1973;1:1396.
4. Nora AH, Nora JJ. A syndrome of multiple congen-
ital anomalies associated with teratogenic expo-
sure. Arch Environ Health 1975;30:17.
5. Rittler M, Paz JE, Castilla EE. VACTERL associa-
tion, epidemiologic definition and delineation. Am
J Med Genet 1996;63:529.
6. Khoury MJ, Cordero JF, Greenberg F, et al. A pop-
ulation study of the VACTERL association: evi-
dence for its etiologic heterogeneity. Pediatrics
7. Czeizel A, Ludanyi I. An aetiological study of the
8. Damian MS, Seibel P, Schachenmayr W, et al. with
the mitochondrial NP 3243 point mutation. Am J
Med Genet 1996;62:398.
9. Kim JH, Kim PCW, Hui CC. The VACTERL associ-
ation: lessons from the Sonic hedgehog pathway.
Clin Genet 2001;59:306.
10. Duhamel D. From the mermaid to anal imperfora-
tion: the syndrome of caudal regression. Arch Dis
11. Subtil D, Cosson M, Houfflin V, et al. Early detec-
tion of caudal regression syndrome: specific inter-
est and findings in three cases. Eur J Obstet Gyne-
col Reprod Biol 1998;80:109.
12. Loewy JA, Richards DG, Toi A. In-utero diagnosis
of the caudal egression syndrome: report of three
cases. J Clin Ultrasound 1987;15:469.
13. Hentschel J, Stierkorb E, Schneider G, et al. Cau-
dal regression sequence: vascular origin? J Perina-
FIGURE 3. Autopsy findings. (A) Photograph shows hypoplasia of
left pelvis and left lower limb. The left knee is in flexion contracture
and left foot hyperextended and rotated. Right clubfoot is evident.
(B) Photograph shows duplicated hallux on the left foot. (C) Left
extremities: photograph shows preaxial polydactyly on the left hand
and duplicated hallux on the left foot. (D) Photograph shows hemi-
vertebrae with scoliosis and hypoplasia with deformity of the tho-
racic and lumbar spine and sacrum, forming a hypoplastic pelvis.
VACTERL AND PARTIAL CAUDAL REGRESSION SYNDROME
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